Structure-activity relationships and activity enhancement techniques of marine bioactive peptides (MBPs).

Marine bioactive peptides (MBPs) are a type of natural compound with a variety of bioactivities, such as anticancer, antimicrobial, antioxidant, and antihypertensive. Due to a wide range of sources, low toxicity, and high specificity, MBPs have now received extensive attention in the fields of food, medicine, and cosmetics. The structure of MBPs determines their biological activities. Therefore, it is essential to analyze the relationship between the structure and bioactivity of MBPs. Because of the advantages of mild conditions, high specificity, safety, and environmental friendliness, enzymatic hydrolysis has become the most commonly used method to produce MBPs. However, the high cost and low yield of enzymatic methods have motivated researchers to search for alternative technologies. Novel pretreatments like ultrasound, microwave, high hydrostatic pressure, and pulsed electric fields have been employed in the production of MBPs. By inducing protein unfolding and increasing enzymatic cleavage sites, these techniques have been demonstrated to accelerate protein hydrolysis and enhance the biological activity of MBPs. This article reviews recent research advances on marine-derived protein hydrolysates and peptides, discusses the relationship between their biological activity and structure, and compares the mechanisms of action of different novel technologies used to promote protein hydrolysis and enhance the biological activity of MBPs. In addition, the current challenges facing the development and application of MBPs are outlined and possible future work in tackling these challenges is also suggested in the current review. It is hoped that this review can promote further development and application of marine active substances.

Deep-learning-based segmentation of perivascular spaces on T2-Weighted 3T magnetic resonance images.

Purpose: Studying perivascular spaces (PVSs) is important for understanding the pathogenesis and pathological changes of neurological disorders. Although some methods for automated segmentation of PVSs have been proposed, most of them were based on 7T MR images that were majorly acquired in healthy young people. Notably, 7T MR imaging is rarely used in clinical practice. Herein, we propose a deep-learning-based method that enables automatic segmentation of PVSs on T2-weighted 3T MR images. Method: Twenty patients with Parkinson's disease (age range, 42-79 years) participated in this study. Specifically, we introduced a multi-scale supervised dense nested attention network designed to segment the PVSs. This model fosters progressive interactions between high-level and low-level features. Simultaneously, it utilizes multi-scale foreground content for deep supervision, aiding in refining segmentation results at various levels. Result: Our method achieved the best segmentation results compared with the four other deep-learning-based methods, achieving a dice similarity coefficient (DSC) of 0.702. The results of the visual count of the PVSs in our model correlated extremely well with the expert scoring results on the T2-weighted images (basal ganglia: rs = 0.845, P < 0.001; rs = 0.868, P < 0.001; centrum semiovale: rs = 0.845, P < 0.001; rs = 0.823, P < 0.001 for raters 1 and 2, respectively). Experimental results show that the proposed method performs well in the segmentation of PVSs. Conclusion: The proposed method can accurately segment PVSs; it will facilitate practical clinical applications and is expected to replace the method of visual counting directly on T1-weighted images or T2-weighted images.

The effect and mechanism of Debaryomyces nepalensis and six strains of winter jujube epiphytic bacteria in building a synthetic community to control post-harvest black spot disease of winter jujube.

The study aimed to develop a synthetic microbial community capable of managing postharvest black spot disease in winter jujube. The research revealed that treatment with Debaryomyces nepalensis altered the surface microbial community, reducing the presence of harmful fungi such as Alternaria, Penicillium, Fusarium, and Botrytis, while boosting beneficial bacteria like Pantoea, Bacillus, Staphylococcus, and Pseudomonas, leading to a decreased decay rate in date fruits. A synthetic community was crafted, integrating D. nepalensis with seven other bacterial strains selected for their abundance, compatibility, culturability, and interactions. This community was refined through homo-pore damage experiments and safety assessments to a final formulation consisting of D. nepalensis and six other bacteria: Bacillus subtilis, Bacillus velezensis, Staphylococcus arlettae, Staphylococcus gallinarum, Pseudomonas sp., and Pseudomonas psychrotolerans. Fruit inoculation tests demonstrated that this synthetic community (6 + 1) significantly lowered the incidence and size of black spot lesions compared to single-strain treatments. By the 10th day of storage, the incidence was 69.23 % lower than the control and 52.94 % lower than the group treated solely with D. nepalensis. Mechanistic studies of the synthetic community's antibacterial effects showed that it can produce volatile compounds, proteases, and ß-1,3-glucanase to inhibit pathogen growth. Additionally, the community forms a biofilm to compete for nutrients and induce jujube resistance to disease.

Automatic segmentation of knee CT images of tibial plateau fractures based on three-dimensional U-Net: Assisting junior physicians with Schatzker classification.

PURPOSE: This study aimed to automatically segment knee computed tomography (CT) images of tibial plateau fractures using a three-dimensional (3D) U-net-based method, accurately construct 3D maps of tibial plateau fractures, and examine their usefulness for Schatzker classification in clinical practice. METHODS: We retrospectively enrolled 234 cases with tibial plateau fractures from our hospital in this study. The four constituent bones of the knee were manually annotated using ITK-SNAP software. Finally, image features were extracted using deep learning. The usefulness of the results for Schatzker classification was examined by an orthopaedic and a radiology resident. RESULTS: On average, our model required < 40 s to process a 3D CT scan of the knee. The average Dice coefficient for all four knee bones was higher than 0.950, and highly accurate 3D maps of the tibia were produced. With the aid of the results of our model, the accuracy, sensitivity, and specificity of the Schatzker classification of both residents improved. CONCLUSIONS: The proposed method can rapidly and accurately segment knee CT images of tibial plateau fractures and assist residents with Schatzker classification, which can help improve diagnostic efficiency and reduce the workload of junior doctors in clinical practice.

[Professor MA Kun treats infertility caused by uterine dysplasia with kidney deficiency and blood stasis].

Uterine dysplasia is a common cause of infertility. Traditional Chinese medicine has unique advantages in the treatment of this disease. This paper introduces a case of infertility caused by uterine dysplasia treated by Professor MA Kun who adopted the therapy of tonifying kidney and activating blood, aiming to summarize the theoretical foundation and formula principles of Professor MA Kun in the clinical treatment of this disease. The kidney stores essence and governs reproduction. Kidney deficiency is the root cause of infertility. The deficiencies in kidney Qi, Yin, and Yang can result in blood stasis to obstruct the uterus, leading to insufficient source for essence and aggravating kidney deficiency. Kidney deficiency and blood stasis affect each other and form a vicious cycle, resulting in uterine dysplasia due to insufficient nutrition and difficult pregnancy. Therefore, Professor MA Kun believes that kidney deficiency and blood stasis is the key pathogenesis of infertility caused by uterine dysplasia and proposes the treatment principle of tonifying kidney and activating blood. Sufficient essence and Qi in the kidney can resolve stasis and generate blood, thus harmonizing Yin and Yang, which can reach thoroughfare and conception vessels to nourish the uterus and recover the normal physiological function of the uterus. In that case, normal pregnancy is possible. Professor MA Kun attaches importance to the therapeutic principle of supplementing Qi and nourishing blood. In addition, she advocates conforming to changes in the menstrual cycle to promote the development of the uterus and the implantation of fertilized eggs. She also integrates traditional Chinese medicine and western medicine to treat both symptoms and root causes. Professor MA Kun's experience has demonstrated definite clinical effect on this disease and can be taken as a reference.

Synergistic ultrasound pulsed electric field extraction of litchi peel polyphenols and determination of their properties.

The effects of pulsed electric field combined with ultrasound (PEF-US) on the recovery of polyphenols from litchi peels were investigated. In addition, the optimal purification parameters for polyphenol extracts and their biological activities were also explored in this study. Single-factor and orthogonal experiments were used to optimize the extraction conditions of polyphenols. After optimization, the total phenol content (TPC) of the sample extracted by PEF-US was 2.30 times higher than that of the sample extracted by traditional hot-water extraction. The mechanism of PEF-US enhancing polyphenol recovery was also revealed by morphological analysis of the powder surface. LX-7 was the best resin by comparing the purification effect of nine macroporous resins. The optimum conditions for purification of litchi peel polyphenols by LX-7 resin were also optimized through adsorption and desorption experiments. UHPLC-MS and HPLC results revealed that gentisic acid, catechin, procyanidin A2 and procyanidin B1 are four main substances in purified samples. The results of bioactivity experiments showed that the purified polyphenol samples had strong antioxidant and antibacterial activity. Overall, PEF-US is an efficient method for recovering polyphenols from litchi peels. Our study also provides a strategy for the comprehensive utilization of fruit processing waste.

Efficacy of Bushen Culuan decoction on ovarian follicle and follicular granulosa cells in mice with premature ovarian insufficiency induced by tripterygium wilfordii polyglycoside.

OBJECTIVE: To investigate the protective efficacy of Bushen Culuan decoction (BCD) on ovarian follicle and follicular granulosa cells in mice with premature ovarian insufficiency (POI) induced by tripterygium wilfordii polyglycoside, and to study the potential mechanism underlying the action. METHODS: Eighty female Balb/c mice were randomly divided into 4 groups (n = 20 each): blank group, model group, Bushen Culuan decoction intervening group (BCD group) and estradiol valerate intervening group (EV group). In the first 14 model establishing d, mice in model group, BCD group and EV group were under Tripterygium wilfordii polyglycoside (TWP) gavage to establish POI models. In the 14-day therapeutic stage, mice in BCD group were taken BCD 18.35 mg·kg-1d-1, mice in EV group were taken EV solution 0.15 mg·kg-1d-1, while mice in blank group and model group were taken normal saline. When the mice accomplished therapy, whole blood was collected for serum hormone including follicle stimulating hormone (FSH), luteal hormone (LH), estradiol (E2), antimullerian hormone (AMH) levels and vascular endothelial growth factor (VEGF), bone morphogenetic protein-7 (BMP-7) measurement. Ovarian tissues were harvested for morphologic observation, follicle counting, ovarian follicular graulosa cell apoptosis test and testing BMP-7 and caspase-3 expressions. RESULTS: The body weights of the mice kept growing stably in the process expect in TWP intervening stage. Compared with model group, BCD group had significantly higher ovarian index, serum E2, AMH, VEGF, BMP-7 levels and significantly lower FSH level (P < 0.05). Meanwhile the VEGF level in BCD group was higher than in EV group (P < 0.05). Compared with model group, the histopathological damage and GCs apoptosis were mitigated; developing follicle counting, BMP-7 expression were up-regulated, and caspase-3 expression was downregulated in BCD groups (P < 0.05). CONCLUSION: BCD treatment could attenuate pathological process in POI ovaries, suppress GC apoptosis, probably through promoting BMP-7 expression and following inhibiting caspase-3 activation.

Associations Between Polybrominated Diphenyl Ethers Concentrations in Human Placenta and Small for Gestational Age in Southwest China.

BACKGROUND: Prenatal exposures to polybrominated diphenyl ethers (PBDEs) may affect fetal growth. Small for gestational age (SGA) is a measure based on birth weight and gestational age at birth and represents a good indicator of fetal growth but it has been used only in a small number of studies. The present study aimed to examine the associations between PBDEs exposure and the risk of SGA among participants from a birth cohort in Southwest China. METHODS: The concentrations of eight common PBDE congeners (BDE-28, BDE47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209) in 996 human placental samples collected between May to October 2020 were determined. A questionnaire survey was administered regarding maternal characteristics. The outcome data of the newborns were obtained from the medical record. The Mann-Whitney U test and binomial logistic regression analysis were used to assess associations between PBDEs concentrations (as a continuous or categorical variable) and SGA. RESULTS: All PBDE congeners were detected in more than 73% of samples. The median concentrations of ΣPBDEs were 10.08 ng/g lipid weight (lw). BDE-209 was the most abundant PBDE congener, contributed 28% to ΣPBDEs. There were 114 (11.4%) SGA infants. The levels of BDE-99, BDE-100, BDE-209, and the total levels of ΣPBDEs in the SGA group were significantly higher than those in the controls. When classifying the PBDEs concentrations as two categories: low and high, high level of ΣPBDEs was associated with increased risk of SGA [odds ratio (OR): 2.203, 95% confidence interval (CI): 1.453-3.340] after adjusting for potential covariates. The association remained significant when stratifying the data by gender of the newborn (OR: 2.572, 95% CI: 1.337-4.947 for boys; OR: 2.385, 95% CI: 1.315-4.325 for girls). CONCLUSION: The present study adds to the literature by using placenta to measure PBDEs exposure during pregnancy, and provides evidence that prenatal exposure to PBDEs may be associated with the risk of SGA, at least at the levels of exposure in our population.

The associations between exposure to trihalomethanes during pregnancy and adverse birth outcomes: A systematic review and meta-analysis.

The study aimed to examine the associations between the level of trihalomethanes and its metabolites in pregnancy and the risks of adverse birth outcomes. We searched the databases of the China National Knowledge Infrastructure, WanFang, Vip, PubMed, and Elsevier Science Direct from database establishment to July 14, 2021 and performed a systematic review and meta-analysis of observational studies reporting associations between trihalomethanes level and abnormally low birth weight and preterm birth. The pooled odds ratio (OR), pooled risk ratio, and pooled risk difference with their 95% confidence interval (CI) were calculated for risk estimates. A total of 24 studies involving 1,118,037 pregnant women were finally enrolled in the present systematic review and meta-analysis. Our research found that abnormally low birth weight was associated with higher levels of total trihalomethanes (OR = 2.45, 95% CI: 1.28, 4.68; P = 0.007). Unexpectedly, the meta-analysis indicated that higher total trihalomethanes level was associated with lower odds of preterm birth (OR = 0.90, 95% CI: 0.81, 0.99; P = 0.03). Our findings indicate that trihalomethanes exposure might be a risk factor for abnormally low birth weight and that it would be prudent to minimize exposure to trihalomethanes during pregnancy because of the risk of abnormally low birth weight. Given some limitations of the systematic review and meta-analysis, our results should be interpreted with caution.

[Effect of therapies for kidney-tonifying and blood-activating in treatment of anovulatory infertility in eugenics].

In the context of the new era, paying attention to maternal and child health and advocating prenatal and postnatal care can effectively improve the quality of the birth population. Traditional Chinese medicine has a long history of prenatal and postnatal healthcare with rich content, which is the theoretical basis of modern related services. With the social development and the improvement of people's awareness of prenatal and postnatal healthcare, people have gradually shifted the focus of prenatal and postnatal healthcare to the peri-pregnancy stage at present, namely that couples of childbearing age are guided to prepare for pregnancy under the premise of solving their basic diseases. Infertility is a common and refractory disease for women of childbearing age. Ovulation disorder is one of its common pathological mechanisms. Traditional Chinese medicine believes that kidney deficiency is the main cause and pa-thogenesis of anovulation infertility and blood stasis is an important factor throughout the disease course. In clinical practice, therapies for invigorating kidney and activating blood are safe and reliable to treat anovulatory infertility mainly by adjusting the hypothalamus-pituitary-ovarian axis, improving ovarian function, uterine environment and gamete quality and increasing endometrial volume. Under the guidance of the thought of prenatal and postnatal healthcare, the authors tried to explore the effect of therapies for kidney-tonifying and blood-activating in the treatment of anovulatory infertility in eugenics, with the purpose of providing ideas and basis for subsequent relevant clinical studies and contributing to prenatal and postnatal healthcare services.

[Study on mechanism of Bushen Culuan Formula in treatment of polycystic ovary syndrome based on network pharmacology and molecular docking].

This study used network pharmacology and molecular docking to study the mechanism of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS). The active ingredients and potential drug targets of Bushen Cu-luan Decoction were obtained by searching the Traditional Chinese Medicine System Pharmacology(TCMSP) database, and the targets of PCOS by searching GeneCards. After the drug targets and disease targets were corrected by Uniprot, the intersection genes were obtained. STRING database and Cytoscape 3.7.2 were used for protein-protein interaction(PPI) analysis of the intersection genes. The ClueGO plug-in of Cytoscape 3.7.2 was employed to perform gene ontology(GO) enrichment and KEGG pathway enrichment for the intersection genes. Finally, molecular docking of the key active ingredients with the targets of Bushen Culuan Formula was performed using AutoDockVina and MGLtools. A total of 136 active ingredients and 314 drug targets of the decoction were obtained from TCMSP, and 136 disease targets from GeneCards. Finally, 49 drug-disease intersection genes were obtained. GO enrichment found that the genes were mainly involved in the regulation of muscle cell apoptosis, positive regulation of small molecule metabolism, core promoter binding, RNA polymerase Ⅱ regulation of pri-miRNA transcription, negative regulation of transmembrane transport and other biological functions. The enriched KEGG pathways mainly included MAPK, PI3 K-Akt, p53, and HIF-1 signaling pathways. The results of molecular docking showed that quercetin and PTGS2 can bind stably and interact through amino acid residues THR206, TRP387, ASN382, etc. This study preliminarily reveals the multi-component, multi-target, and multi-pathway mechanism of Bushen Culuan Formula in the treatment of PCOS-related infertility, which provides a basis for further research.

Cough Inhibition Activity of Schisandra chinensis in Guinea Pigs.

Chronic cough is very common in respiratory clinics, and no effective drugs are available. Schisandra chinensis (Turcz.) Baill. (S. chinensis), an important traditional Chinese medicine, has been extensively prescribed for patients with a persistent cough. Preliminary research indicated that 95% ethanol extracts (EE) of S. chinensis showed remarkable antitussive activity in guinea pigs exposed to cigarette smoke (CS). To find out the antitussive ingredients of S. chinensis, EE was divided into four fractions according to the polarity: petroleum ether extract (PEE), ethyl acetate extract (ECE), n-butyl alcohol extract, and residue extract. The antitussive, antioxidant, and anti-inflammatory effects of the four fractions were evaluated in a guinea pig model of cough hypersensitivity induced by CS exposure. Eighteen main constituents of the two effective fractions, PEE and ECE, were identified using ultra-high-pressure liquid chromatography electronic spray ion time-of-flight mass spectrometry. The cough inhibition activities of compound 1, 3, 9, 10, 17 were evaluated on citric acid induced acute cough guinea pigs. The results showed that the antitussive activity of EE was almost all contained in PEE and ECE. The 16 major peaks in PEE were identified as 15 lignans (1-12 and 14-16) and 1 triterpene (compound 13), and 3 major peaks (1, 17, and 18) in ECE were also identified as lignans. Three doses of five compounds brought about a significant decrease in number of cough efforts (P < .01), and the cough inhibition rates were between 40.9% and 85.1%. Therefore, lignans are the antitussive ingredients of S. chinensis.

[Establishment of premature ovarian insufficiency kidney deficiency and blood stasis pattern mouse model with Tripterygium wilfordii polyglycoside for Bushen Culuan Decoction therapy].

To establish a mouse model of premature ovarian insufficiency( POI) with kidney deficiency and blood stasis pattern by Tripterygium wilfordii polyglycoside( TWP) gavage,and to evaluate the ovarian function and fertility of the model,in order to find Bushen Culuan Decoction therapeutic mechanism. 60 SPF level Blab/c female mice with normal estrous cycle were randomly divided into 6 groups of 10 each: blank group 1( BG1),blank group 2( BG2),blank fertility group( BFG),model group( MG),model recovery group( MRG) and model fertility group( MFG). The mice in three model groups were treated by gastric gavage with TWP suspension 40 mg·kg-1 twice a day for 14 days,while the mice in three blank groups were treated by gastric gavage with same volume normal saline for 14 days. The mice in BG1 and MG were sacrificed and dissected on day 15. The mice in BG2,BFG,MRG and MFG were returned normal feeding from day 15 and were sacrificed and dissected on day 29. The mice in BFG and MFG were cohabited with male mice with a ratio of 2 ∶1( female ∶male) from day 15. The general situation and estrous cycles of all mice were observed every day. Serum sex hormone levels,ovarian index,uterine index,ovarian morphology,follicle count,ovarian VEGF and ES index were observed within the mice in BG1,BG2,MG and MRG. Pregnancy rate,litter size,survival number of newborn mice and male-female proportion were reported within the mice in BFG and MFG. In model establishing stage,the body weight of mice significantly decreased( P <0. 05) in MG and MFG. Compared with BG1,the mice in model group had irregular estrous cycle,decreased ovarian and uterine indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression and decreased ES expression( P <0. 05). Compared with blank group 2,the mice in model recovery group had irregular estrous cycle,increased FSH level,decreased ovarian indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression( P<0. 05). Compared with blank fertility group,the mice in model fertility group had smaller litter size and newborn mice survival count( P<0. 05). Gastric gavage with TWP 40 mg·kg-1 twice a day for 14 days is a feasible way to establish a POI kidney deficiency and blood stasis pattern mouse model. The mice ovarian functions didn't recovery on day 14 after stopping TWP intervening,which could suggest the effectiveness of subsequent therapeutic intervention.

[Systematic review and Meta-analysis of effect of Yinzhihuang Oral Liquid in treatment of neonatal jaundice].

To systematically review effectiveness and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice. A systematic retrieval was performed throughout China National Knowledge Infrastructure( CNKI),Wan Fang,VIP,Sino Med and PubMed,Medline,Cochrane Library databases from the establishment to April 2019. Randomized controlled trials of Yinzhihuang Oral Liquid in treatment of neonatal hyperbilirubinemia were retrieved. Clinical studies in line with the inclusion criteria were involved for data extraction,and the quality of the included literatures was evaluated by the risk bias assessment tool in the Cochrane review manual. Finally,Meta-analysis was performed by Rev Man 5.3 software. A total of 30 studies were involved,involving 3 923 child patients,including1 940 in observation group and 1 983 in control group. According to the results of Meta-analysis,the total effective rate( RR = 1. 22,95%CI[1. 18,1. 26],P<0. 000 01),level of TBi L after treatment( MD =-38. 78,95%CI[-48. 38,-29. 18],P<0. 000 01),time to jaundice resolution( MD =-1. 76,95% CI[-2. 10,-1. 41],P < 0. 000 01) and daily average decrease value of bilirubin( MD =11. 67,95%CI[8. 89,14. 45],P<0. 000 01) of observation group were significantly better than those of control group,with statistically significant differences. Adverse reactions were reported in nine studies,mainly including diarrhea,vomiting,fever,rash and other symptoms,which did not affect the treatment effect. The effectiveness of Yinzhihuang Oral Liquid combined with conventional therapy in treating neonatal jaundice was better than conventional therapy alone,with little adverse reactions. However,most of literatures included had a low research quality,which impacted the reliability of the conclusion. Therefore,it is suggested to conduct more largesample-size,multicenter,scientifically designed,strictly implemented high-quality randomized controlled trials in the future,in order to study the efficacy and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice.